RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in rat bone and growth plate cartilage.
Using differential display polymerase chain reaction, we cloned a novel cDNA named RoBo-1 from rat tibia. RoBo-1 is abundantly expressed in bone, including the hypertrophic chondrocytes of the growth plate where cartilage is remodeled into bone. RoBo-1 mRNA expression increased in response to two modulators of bone metabolism, estradiol and intermittent mechanical loading, suggesting a role in bone homeostasis. The 1.6-kilobase cDNA encodes a 240-amino acid protein with a cysteine spacing pattern, suggesting that RoBo-1 is a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family. Furthermore, the C-terminal contains a glycosyl-phosphatidylinositol attachment site, suggesting that it is a cell surface protein similar to other mammalian members of this family. The strongest homology of RoBo-1 is to the snake serum-derived phospholipase A2 inhibitors, which uniquely contain two of the cysteine domains but are secreted proteins. Interestingly, RoBo-1 is likely the first membrane-anchored member of this family containing two cysteine domains. Thus, the tissue specificity, responsiveness to bone protective mediators, along with its relationship to the multifunctional urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family suggests that RoBo-1 may play a novel role in the growth or remodeling of bone.
Noel
L S
LS
Department of Molecular Pharmacology, Glaxo Wellcome Research, Research Triangle Park, North Carolina 27709, USA.
Champion
B R
BR
Holley
C L
CL
Simmons
C J
CJ
Morris
D C
DC
Payne
J A
JA
Lean
J M
JM
Chambers
T J
TJ
Zaman
G
G
Lanyon
L E
LE
Suva
L J
LJ
Miller
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D003001:Cloning, Molecular; D003545:Cysteine / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006031:Glycosylation; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
C524900:Plaur protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D004958:Estradiol; D003545:Cysteine